The proposed research will concern the effects of high hydrostatic pressures, in the range of 1 to 3,000 atmospheres, upon macromolecular aggregates in solution. On one hand, we shall carry out a more thorough examination of the effects of pressure upon simple oligomeric proteins stressing the kinetics of the approach to equilibrium. The aim here will be to extend and better quantitate the observations of the conformational drift of separated subunits, the discovery of which has been the main outcome of our research in this subject for the past six years. On the other hand we will extend the study of the effects of pressure to the icosahedral viruses. Preliminary studies indicate that dissociation under pressure and reassociation upon decompression take place with appearance of evidently modified virus capsids. The differences between the native viruses and the species recovered after decompression will be examined as regards the role of the conformational drift in the formation of the modified aggregates. Their infectivity and immunogenic properties will be studied in detail in relation to the possibility of obtaining materials suitable for vaccination. The title of past grants (GM11223 1-24) reflected the development of fluorescence methodology. In the coming period we shall continue to use fluorescence techniques which have already proven indispensable to the present purpose, but I have changed the title to indicate our preoccupation with a well defined objective.